One finding emerging from our research program is that insult to the medial temporal lobe in monkeys, and more specifically the amygdala, results in an array of behavioral changes that mimic in many ways the behavioral disturbances seen in autistic people. The goal of the present project is to pursue our investigation of this putative animal model of autism by testing the effects of early versus late lesions of a neural network that includes the amygdala and orbitofrontal cortex. For this purpose, using newly developed neurosurgical procedures and behavioral tasks, we will first evaluate the effects of selective bilateral lesions of the orbitofrontal cortex and amygdala in adult monkeys on cognitive tasks, fearful responses, and social bonds. Second, we will follow the long-term effects of early selective bilateral lesions of the orbitofrontal cortex and amygdala on cognitive tasks, fearful responses, and social bonds in the developing monkeys. These studies will provide the unique opportunity to examine in the same animals cognitive functions, regulations of emotions, and formation and maintenance of social bonds. Also, these studies will allow direct comparison between early versus late lesions that may indicate whether the early lesions he a beneficiary or a more debilitating behavioral effects. Impairment in monkeys with these early and late lesions will be compared to that of participants with autism (Project I). Finally, the monkeys will participate in Project II Aim 2 and Project IV to establish the impact of these lesions on brain systems distant from the neural insult, such as prefrontal cortex and cingulate. Through, such research, principles of the brain's response to damage will ultimately advance our understanding of the basic development processes that follow early dysfunction of the orbitofrontal-limbic circuit in primates, its implication for developmental disorders, such as autism, and leads eventually to discovery of ways by which such effects can be alleviated or even eliminated.